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Objective To compare the duration of mechanical ventilation between preterm infants receiving closed-loop automated oxygen control (CLAC) or manual oxygen control.Design Randomised controlled trial.Setting Tertiary neonatal unit in London, UK.Patients Infants (n=69) with a median (IQR) gestational age of 27.0 (25.6–29.0) weeks studied at a corrected postmenstrual age of 27.6 (25.9–29.1) weeks.Interventions Infants were randomised to CLAC or manual oxygen control within 48 hours of initiation of mechanical ventilation if less than 7 days of age until successful extubation.Main outcome measures Duration of mechanical ventilation.Results The CLAC infants (n=34) compared with those who received manual control had a shorter duration of mechanical ventilation (median (range): 11 (1–57) vs 40 (3–134) days, p=0.027), a shorter duration of supplemental oxygen (median (range): 33 (0–100) vs 47 (3–335) days, p=0.031), a lower incidence of bronchopulmonary dysplasia (BPD) at 36 weeks postmenstrual age (55% vs 83.9%, p=0.015) and fewer required home oxygen (26.5% vs 51.4%, p=0.016). In the CLAC infants, the time spent in the target oxygen range (91%–95%) was increased (p<0.001) and the times spent in hypoxaemia (peripheral oxygen saturation level (SpO 2)<85%) and hyperoxaemia (SpO2>95%) were reduced (p<0.001).Conclusions Use of CLAC in preterm, ventilated infants was associated with improved achievement of oxygen saturation targets, shorter durations of mechanical ventilation and supplemental oxygen treatment and a lower incidence of BPD. These results need to be replicated in larger multicentre studies before any change in routine practice could be recommended.Trial registration number NCT05030337.